The impact of dietary arginine and citrulline in the neonatal gut

Hurley, Martin Fredrick (2023) The impact of dietary arginine and citrulline in the neonatal gut. Masters thesis, Memorial University of Newfoundland.

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Abstract

Citrulline is a non-protein amino acid that is converted to arginine in the urea cycle through the activities of argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL); as such, citrulline supplementation may increase arginine availability. Arginine deficiency in preterm infants is associated with the serious gastrointestinal infection, necrotizing enterocolitis (NEC). Low arginine may contribute to NEC via inadequate nitric oxide (NO) synthesis, which would impair blood flow to the gut. Arginine is converted to NO by nitric oxide synthase (NOS), but citrulline may be a more effective precursor of NO, as ASS and ASL are co-localized with NOS. Preterm infants are more susceptible to NEC during the transition from parenteral nutrition (PN) to enteral feeding. In piglets with PN-induced intestinal atrophy, we hypothesized that supplemental citrulline would lead to greater NO production and higher blood flow to the intestine. Piglets (7-10 days, n = 20) received venous and gastric catheters and a probe to measure superior mesenteric artery (SMA) blood flow. Intestinal atrophy was induced with PN feeding. On day 4, piglets were randomized to enteral refeeding of an elemental formula with arginine concentration equivalent to 1) sow milk (Low Arg), 2) 2.5 times sow milk (High Arg) or 3) Low Arg plus citrulline (Cit) with arginine plus citrulline equimolar to High Arg. At the initiation of enteral feeding, SMA blood flow was measured for 10 hours. On day 5, whole body protein and NO synthesis were measured with tracers. Whole body protein synthesis was highest in High Arg group compared to Low Arg and Cit groups, suggesting that the concentration of dietary arginine supplied by milk does not meet the whole body needs of a neonate with compromised intestinal function; furthermore, citrulline was not able replace arginine for protein synthesis. NO synthesis and SMA blood flow were highest in the Cit group, suggesting that citrulline was a better precursor for NO synthesis than arginine, and supported better blood flow to the gut. Citrulline supplementation with arginine at concentrations greater than that in milk may be a means to improve arginine status and enhance intestinal recovery in neonates who are at high risk for NEC during the transition from parenteral to enteral feeding.

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